The therapeutic objective as regards obesity is well defined; it is a matter either of allowing the individual to lose a significant amount of weight, or of helping the individual to maintain a weight level, which is as low as desired. Several types of approaches have been envisaged to date. The prevalence of obesity in adults, children and adolescents has increased rapidly over the past 30 years in the United States and globally, and continues to rise. Obesity is classically defined based on the percentage of body fat or, more recently, the body mass index (BMI), also called Quetlet index (National Task Force on the Prevention and Treatment of Obesity, Arch. Intern. Med., 160: 898-904 (2000); Khaodhiar, L. et al., Clin. Cornerstone, 2: 17-31 (1999)). The BMI is defined as the ratio of weight (kg) divided by height (in meters) squared.
Overweight and obesity are associated with increasing the risk of developing many chronic diseases of aging seen in the U.S. (Must, A. et al., JAMA, 282: 1523-9 (1999)). The key to reducing the severity of the diseases is to lose weight effectively. Although about 30 to 40% claim to be trying to lose weight or maintain lost weight, current therapies appear not to be working. Besides dietary manipulation, pharmacological management and in extreme cases, surgery, are sanctioned adjunctive therapies to treat overweight and obese patients (Expert Panel, National Institute of Health, Heart, Lung, and Blood Institute, 1-42 (June 1998); Bray, G. A., Contemporary Diagnosis and Management of Obesity, 246-273 (1998)). Drugs have side effects, and surgery, although effective, is a drastic measure and reserved for morbidly obese. Nutritional approaches are directed toward reducing the supply of energy in the form of foods. This can be achieved either by drastically reducing the energy supplies or by replacing high-energy nutrients with others, which are lower in energy such as indigestible substitute fats, structured triglycerides that are difficult to assimilate or dietary fibers that cannot be assimilated.
5-HTP (5-Hydroxytryptophan) is a direct precursor of serotonin. 5-HTP is a natural compound isolated from the seeds of an African plant called Griffonia simplicifolia, grown mostly in Ghana and the Ivory Coast. It can also be made synthetically in the laboratory. Its toxicity is extremely low as noted by lethal dose (LD) studies. Studies conducted in the rat and mice have demonstrated that the LD50 is negligible as compared to therapeutic doses: LD50 per os and i.p. in the mouse 2500 mg/kg and 1400 mg/kg respectively. However, synthetically produced 5-HTP has been associated with a cluster of symptoms called eosinophilia-myalgia syndrome (EMS). EMS is a serious systemic illness characterized by elevations of certain white blood cells and severe muscle pain. In 1989 there was an epidemic outbreak of EMS, triggered by the consumption of synthetically prepared L-tryptophan produced by a fermentation process. More than 1,500 cases including at least 37 deaths were reported to the CDC as of February, 2001. 5-HTP isolated from the seeds of Griffonia simplicifolia does not require the use of a fermentation process and is a safer product.
Policosanol is a mixture of primary aliphatic alcohols isolated from plant waxes such as sugarcane. The aliphatic alcohol of the mixture is a CH3—(CH2)n—CH2OH alcohol with chain length varying from 24 to 39 carbon atoms. Typical aliphatic alcohols of the mixture are octacosanol, hexacosanol, heptacosanol, triacontanol and dotriacontanol. Policosanol has been shown to lower cholesterol in animal models, healthy volunteers, and patients with type II hypercholesterolemia. Therefore, it is useful in the dyslipidemia associated with type 2 diabetes mellitus.
Green tea has long been known to have an effect on body weight and energy expenditure. Epigallocatechin gallate (abbreviated herein as EGCG) is a naturally occurring substance found chiefly in green tea and its extracts. EGCG is ideal as a weight loss agent because of its lack of toxicity or apparent side effects. EGCG and related catechins occur naturally in several types of plants, including tea, and thus have a long history of safety in that form. Recently, the anorectic effects of green tea have been attributed to polyphenols, especially the most abundant one-EGCG (Dulloo A G, et al. Am J Clin Nutr 1999; 70:1040-5). The thermogenesis effect of EGCG has also been shown to be dependent on the sympathetically released norepinephrine (NE) in the activation of peripheral thermogenesis (Dulloo A G. et al. Int J Obes Relat Metab Disord 2000; 24:252-8). These studies indicate that it is not EGCG alone, but the combination of EGCG and caffeine via their interaction with sympathetically released NE that confers green tea with its ability to enhance thermogenesis. The mechanisms behind these synergistic interactions are to be expected because EGCG and caffeine act in concert along different control points underlying NE-induced thermogenesis. EGCG inhibits the enzyme catechol-O-methyltransferase that degrades NE within the synaptic cleft (Borchardt R T, Huber, J A, J Med Chem 1975; 18:120-2), whereas caffeine inhibits primarily the phosphodiesterase enzyme complex that degrades cyclic AMP, the intracellular secondary messenger for NE-mediated thermogenesis. The result is that two feedback inhibition pathways along the pathway of NE-activated thermogenesis have been removed. One would therefore expect the combination of EGCG and caffeine to be more effective than either compound alone in potentiating thermogenesis under sympathetic neural control.
US publication no. 20020192308 discloses an appetite suppressant comprising green tea; green tea leaf extract; and a chromium additive. US publication no. 20030143287 discloses a nutritional supplement for overweight and obese individuals, comprising a low-glycemic-index carbohydrate source, a source of protein and a source of fat; wherein the amounts of carbohydrate, protein and fat are sufficient for use in individuals to aid in the management of weight loss. US publication no. 20030162725 describes a pharmaceutical composition comprising an effective amount of a compound which enhances serotonin-mediated neurotransmission, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from the group consisting of precursors of serotonin, pro-drugs of serotonin, or an intermediate in the biosynthesis of serotonin and a compound that promotes thermogenesis, wherein said compound is selected from the group consisting of epigallocatechin gallate or derivatives thereof. U.S. Pat. No. 6,565,896 discloses a cholesterol treatment composition comprising an effective amount of: Green Tea extract comprising standardized 98% polyphenols, 80% catechins; 45% EGCC; Gamma Oryzanol; Gugulipids; Beta Sitosterol; Artichoke extract standardized for 5% cynarine; Grape Seed extract comprising by weight 54% proanthocyanidin dimer, 13% proanthocyanidin trimer, 7% proanthocyanidin tetramer, and 6% monomer; Chromium; Pantethine; and Policosanol. US publication no. 20050256178 discloses a composition comprising biotin in an amount sufficient to administer to a subject a daily dosage of 0.01 mg per kg body weight to about 3 mg per kg body weight and at least one additional component selected from the group consisting of pantethine or a metabolite thereof, EGCG, phytanic acid, lipoic acid and policosanol.
US publication no. 20060078627 describes a composition for treatment of obesity or generally aiding weight loss, comprising: L-phenylalanine, caffeine, and one or more of the group of all forms of 5-hydroxytryptophan and L-tryptophan, all from either natural or synthetic sources. US publication no. 20060045913 describes a bi-layer tablet for the treatment of conditions associated with serotonin deficiencies in the nervous system characterized by the fact that at least one layer contains tryptophan and/or its metabolites, one of said layers under physiological conditions being a fast layer which possesses a rapid release rate and the other layer having a retarded release rate. US publication no. 20060078627 discloses a nutritional composition which promotes fast weight loss, burns calories, increases thermogenesis, supports energy metabolism and/or suppresses appetite in individuals, the nutritional composition comprising Garcinia cambogia extract, Gymnema sylvestre leaf extract, and green tea leaf extract. PCT publication no. WO2004041257 describes a composition for the treatment or prevention of type 2 diabetes in those individuals with pre-diabetes, or impaired glucose tolerance (IGT) or obesity comprising at least two components selected from EGCG, pantethine or a metabolite thereof, phytanic acid, lipoic acid, policosanol and coenzyme Q. U.S. Pat. No. 6,383,482 discloses a weight loss composition comprising effective amounts of: green tea extract; hydroxycitric acid; 5-hydroxytryptophan; glucomannan; chromium picolinate; and Lactobacillus acidophilus. 
Overweight and obesity are associated with other chronic diseases such as type 2 diabetes mellitus, hypertension, coronary heart diseases and dyslipidemia, gallstones and cholecystectomy, osteoarthritis, cancer (of the breast, colon, endometrial, prostate, and gallbladder), and sleep apnea. It is estimated that there are around 32500 deaths annually that are attributable to obesity. The key to reducing the severity of the diseases is to lose weight effectively. Besides dietary manipulation, pharmacological management and in extreme cases, surgery, are sanctioned adjunctive therapies to treat overweight and obese patients (Expert Panel, National Institute of Health, Heart, Lung, and Blood Institute, 1-42 (June 1998); Bray, G. A., Contemporary Diagnosis and Management of Obesity, 246-273 (1998)). Drugs have side effects, and surgery, although effective is a drastic measure and reserved for morbidly obese. The present invention preferably provides anti-obesity compositions and method of manufacturing such novel compositions, which promote fast weight loss, burns calories, increase thermogenesis, support energy metabolism and/or suppress appetite in individuals. The compositions of the present invention comprise preferably natural product(s) as active agent(s) and are highly safe and effective, besides being economical to manufacture.